Microbiology spectrum最新文献

{"title":"Identification of OxyR as an activator of type 1 fimbriae (<i>fim</i>) in <i>Salmonella enterica</i> serovar Typhi.","authors":"Karine Dufresne, Camille Ou, Melvina Badet, Gabrielle Cadieux, France Daigle","doi":"10.1128/spectrum.03267-24","DOIUrl":"https://doi.org/10.1128/spectrum.03267-24","url":null,"abstract":"<p><p><i>Salmonella enterica</i> serovar Typhi (<i>S</i>. Typhi) encodes 14 fimbrial gene clusters, including the mannose-binding type 1 fimbriae known as Fim. Type 1 fimbriae have been implicated in biofilm formation and adhesion to host cells in <i>Salmonella</i>. However, their regulation in <i>S</i>. Typhi remains largely unknown. To identify genes affecting the regulation of <i>fim</i> in <i>S</i>. Typhi, we employed both a targeted and a genome-wide transposon-based screening approach. Overall, we identified 18 potential regulators of <i>fim</i> expression: 10 activators and 8 repressors. Two genes involved in the electron transport chain, <i>yqiC</i> and <i>ndh,</i> which encode the type II NADH dehydrogenase NDH-2, were identified. Both YqiC and NDH-2 contribute to the production of reactive oxygen species, prompting an investigation into the roles of oxidative stress response regulators OxyR and SoxR. We found that only OxyR regulates <i>fim</i> expression, which was specific to <i>S</i>. Typhi. OxyR acts by directly binding to the <i>fimA</i> promoter region. This study paves the way for future development of anti-adhesion strategies through the identification of 14 novel regulators for the most prominent fimbriae of <i>S</i>. Typhi.IMPORTANCEAdhesion mediated by fimbriae is one of the critical steps in the infection process. Therefore, it is essential to better understand the regulation of type 1 fimbriae (<i>fim</i>) in the human-specific pathogen <i>Salmonella enterica</i> serovar Typhi, the etiologic agent of typhoid fever. In this study, we identified 18 distinct mutants with altered regulation of <i>fim</i>. Furthermore, we confirmed that the DNA-binding protein OxyR directly regulates <i>fim</i> expression. Importantly, we also demonstrated regulatory differences in <i>fim</i> expression between <i>S</i>. Typhi and <i>S</i>. Typhimurium, as six of the genes identified altering <i>fim</i> expression in <i>S</i>. Typhi either did not affect <i>fim</i> expression in <i>S</i>. Typhimurium or had the contrary effect. This highlights fundamental differences between these serovars and emphasizes the need to investigate and compare aspects of gene regulation in <i>S</i>. Typhi.</p>","PeriodicalId":18670,"journal":{"name":"Microbiology spectrum","volume":" ","pages":"e0326724"},"PeriodicalIF":3.8,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combined oropharyngeal nasal (ON) swabs for the molecular detection of respiratory pathogens including <i>M. pneumoniae</i> in symptomatic children.","authors":"Hannah Nelson, Iryna Kayda, Nicole Watson, Mai-Lei Woo Kinshella, Jennifer Cochrane, Neil Desai, Michelle Dittrick, Linda Hoang, Michael T Hawkes, Garth Meckler, Vikram Sabhaney, Jonathan B Gubbay, Miguel Imperial, Jocelyn A Srigley, Lynne Li, David M Goldfarb","doi":"10.1128/spectrum.02181-25","DOIUrl":"https://doi.org/10.1128/spectrum.02181-25","url":null,"abstract":"<p><p>This study aimed to evaluate the diagnostic yield and acceptability of parent-/caregiver-collected oropharyngeal nasal (ON) swabs compared with healthcare worker (HCW)-collected nasopharyngeal (NP) swabs for detecting respiratory viruses and <i>Mycoplasma pneumoniae</i> in children. Symptomatic children (0-4 years) presenting to the BC Children's Hospital Emergency Department provided HCW-collected NP and caregiver-collected ON swabs. Acceptability was assessed using a 5-point Likert scale. Samples were tested using the SARS-CoV-2/Influenza A + B/RSV GeneXpert assay, and a subset was tested on the BioFire respiratory panel (RP) 2.1 during the initial research phase. In a subsequent implementation phase during a high incidence of <i>M. pneumoniae</i>, paired ON and NP swabs were collected and tested on the RP 2.1 in a quality improvement initiative. All <i>M. pneumoniae</i>-positive samples underwent testing for cycle threshold values. We analyzed 139 pairs from the research phase and 219 from the implementation phase. Detection rates for SARS-CoV-2, influenza A/B, and RSV were similar across swab types. Of 273 pairs tested on BioFire, ON swabs demonstrated significantly higher detection of <i>M. pneumoniae</i> (sensitivity of 94%, confidence interval [CI] [86, 98] ON vs 64% [61-75] NP, <i>P</i> = 0.0020) and comparable detection for other pathogens. Caregivers rated ON swab collection as more acceptable than NP swabs (median 4.5 [4-5] vs 2 [IQR 1-3], <i>P</i> < 0.0001). ON swab performance was similar to NP swabs for the detection of respiratory viruses and showed improved diagnostic yield of <i>M. pneumoniae</i>. Given their higher acceptability ratings, ON swabs should be considered as a less-invasive diagnostic option for children.IMPORTANCEThe current clinical standard for diagnosing respiratory infections in children typically requires a nasopharyngeal (NP) swab, which may be uncomfortable for the patient and must be collected by a healthcare worker. This study presents a less-invasive option, an oropharyngeal nasal (ON) swab collected by a parent or caregiver, that has comparable detection for common respiratory viruses and improved detection for <i>Mycoplasma pneumoniae</i>, a common but treatable cause of childhood pneumonia. Additionally, parents/caregivers rated ON swabs as significantly more acceptable than NP swabs on a scale of 1 to 5. Given the increased acceptability and superior detection of treatable <i>M. pneumoniae</i>, ON swabs are a patient-centered alternative to NP swabs and should be considered as a preferred diagnostic option for children.</p>","PeriodicalId":18670,"journal":{"name":"Microbiology spectrum","volume":" ","pages":"e0218125"},"PeriodicalIF":3.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145040702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Positivity analysis of <i>Bordetella</i> spp. and SARS-CoV-2 coinfections in clinical samples from Colombia, 2021-2022.","authors":"Valentina Bonilla-Bravo, Efrain Montilla-Escudero, Ximena Castro Martinez, Fabiola Rojas, Carolina Duarte, Sandra Aparicio, Sergio Yebrail Gómez-Rangel, Paula Rodriguez Romero, Sandra Lucero Bonilla, Franklyn Prieto Alvarado, Jaid Rojas Sotelo, Gloria Rey Benito","doi":"10.1128/spectrum.01242-25","DOIUrl":"10.1128/spectrum.01242-25","url":null,"abstract":"<p><p>Pertussis and COVID-19 are respiratory diseases with similar clinical manifestations, complicating diagnosis. In Colombia, pertussis surveillance is based on probable cases confirmed through laboratory detection of <i>Bordetella pertussis</i>. During the COVID-19 pandemic, pertussis incidence declined sharply. Given limited data on coinfections with COVID-19 and pertussis, this study aimed to estimate the positivity of <i>Bordetella</i> spp. in SARS-CoV-2-positive samples collected in Colombia during 2021-2022. A retrospective analysis was conducted on samples collected between January 2021 and December 2022 through simple random sampling from specimens stored at the National Reference Laboratory (NRL). Demographic data, symptoms, complications, and race were obtained from the National Surveillance System (SIVIGILA), and PCR results were used to identify <i>Bordetella</i> spp. coinfections. National and departmental positivity rates were estimated with Clopper-Pearson confidence intervals. PCR testing for <i>Bordetella</i> spp. was positive in 0.54% (6/1,102) of samples, with four cases involving B. pertussis and two involving <i>B. parapertussis</i>; no <i>B. holmesii</i> coinfections were detected. The national positivity rate of SARS-CoV-2 and <i>Bordetella</i> spp. coinfections was 1.92% in 2021, decreasing to 1.25% in 2022. Although coinfections with viral agents and <i>B. pertussis</i> are common, this study found low positivity of SARS-CoV-2 and <i>Bordetella</i> spp. coinfections in Colombia during 2021-2022, likely due to non-pharmacological interventions, the cyclical pattern of <i>B. pertussis</i>, and possible underestimation related to the geographic and demographic scope of the sample. This is the first report of such coinfections in Colombia, offering a reference for future studies in Latin America.IMPORTANCEThis is the first report of SARS-CoV-2 and <i>Bordetella</i> spp. coinfections in Colombia, providing key evidence of their low occurrence during 2021-2022. Given that both diseases share clinical features and may complicate differential diagnosis, these findings underscore the importance of integrated surveillance for respiratory pathogens. The observed decrease in positivity may be linked to non-pharmaceutical interventions and the cyclical nature of pertussis, while also highlighting potential limitations in the geographic and demographic representativeness of the sample. This study offers a valuable baseline for future research in Latin America and reinforces the need to strengthen diagnostic capacity to detect coinfections, particularly in epidemic or pandemic contexts.</p>","PeriodicalId":18670,"journal":{"name":"Microbiology spectrum","volume":" ","pages":"e0124225"},"PeriodicalIF":3.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145040036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of MorI/MorR quorum sensing in <i>Methylobacterium oryzae</i> CBMB20: modulating bacterial functions for enhanced adaptability.","authors":"Qiying Deng, Yue Zheng, Huagui Gao, Haofang Wu, Enyu Shi, Mengmeng Cheng, Huishan Wang, Lisheng Liao","doi":"10.1128/spectrum.02117-25","DOIUrl":"https://doi.org/10.1128/spectrum.02117-25","url":null,"abstract":"<p><p>The quorum-sensing (QS) system in <i>Methylobacterium oryzae</i> CBMB20, an endophytic bacterium associated with rice (<i>Oryza sativa</i> L.), plays a critical role in regulating bacterial behaviors essential for plant growth promotion and adaptation. This study aimed to elucidate the functional role of the MorI/MorR QS system in <i>M. oryzae</i> CBMB20 and its potential application as a bioinoculant. We identified and characterized two QS signals, 3-OH-C12-HSL and 3-oxo-C12-HSL, synthesized by the MorI enzyme. The MorR receptor was found to preferentially respond to 3-OH-C12-HSL, indicating a high degree of specificity in QS signaling. The deletion mutants of <i>morI</i> and <i>morR</i> exhibited significant changes in exopolysaccharides (EPS), motility, and methanol utilization, suggesting that the MorI/MorR system is crucial for bacterial survival and adaptation. Transcriptome analysis revealed that MorR acts as a repressor, controlling the expression of numerous genes, many of which are upregulated upon its deletion. Our findings highlight the multifaceted role of the MorI/MorR QS system in <i>M. oryzae</i> CBMB20, influencing key biological functions such as EPS production, motility, and methanol utilization. The modulation of these traits through QS could enhance the bacterium's effectiveness as a bioinoculant for promoting plant growth. This study contributes to the understanding of how QS systems can be harnessed to improve the efficacy of plant growth-promoting bacteria in agricultural settings, offering insights into the potential for genetic manipulation to optimize bioinoculant performance.</p><p><strong>Importance: </strong>This study provides critical insights into microbial communication by functionally characterizing the MorI/MorR quorum-sensing (QS) system in <i>Methylobacterium oryzae</i> CBMB20, a plant-beneficial methylotroph. We identify 3-OH-C12-AHL as a key long-chain signal governing exopolysaccharides biosynthesis, swimming motility, and methanol metabolism traits pivotal for host colonization. These findings not only elucidate novel regulatory mechanisms in plant-associated bacteria but also pave the way for engineering QS-driven strategies, such as synthetic consortia or targeted microbiome interventions, to enhance sustainable agricultural practices.</p>","PeriodicalId":18670,"journal":{"name":"Microbiology spectrum","volume":" ","pages":"e0211725"},"PeriodicalIF":3.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145040515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional characterization and membrane localization of the styrene oxide isomerase from <i>Rhodococcus opacus</i> 1CP and <i>Zavarzinia compransoris</i> Z-1155.","authors":"Selvapravin Kumaran, Shanice Olanipekun, Latife Sönmez, Lars Janzen, Peter-Leon Hagedoorn, Dirk Tischler","doi":"10.1128/spectrum.01526-25","DOIUrl":"https://doi.org/10.1128/spectrum.01526-25","url":null,"abstract":"<p><p>Styrene oxide isomerase (SOI) is a part of the styrene degradation enzyme complex, performing the isomerization of toxic intermediate styrene oxide into phenylacetaldehyde. For many years, the enzyme was believed to be cofactor-independent, and hence, the mechanism of this enzyme was proposed to be acid-base catalysis. Recently, the presence of heme was identified and reported in SOI from <i>Pseudomonas</i> sp. VLB120. Alongside, the membrane localization was also postulated since its discovery but lacks experimental proof. In this study, we highlight the localization of SOIs from two bacterial strains, <i>Rhodococcus opacus</i> 1CP and <i>Zavarzinia compransoris</i> Z-1155, heterologously overproduced in the cell membrane of <i>E. coli via</i> sfGFP-tagged fusions. In addition, the site-directed mutagenesis of acidic and basic amino acids in SOI from 1CP also showcased that histidine-57 is the axial ligand to the heme. Electron paramagnetic resonance (EPR) and biocatalytic assays showed arginine-111 possibly coordinating the propionate group of heme. The functional assays of differently tagged sfGFP with and without linkers, and the truncation of the terminal extension of SOI from 1CP and Z-1155, indicate their possible role in proper substrate channeling. It also supports the previously proposed SOI role as a membrane anchor for other enzymes in styrene degradation pathway.</p><p><strong>Importance: </strong>Styrene oxide isomerase (SOI) catalyzes the isomerization of styrene oxide into phenylacetaldehyde in the side chain oxygenation of the styrene degradation pathway. Despite performing a key role in this pathway, the biology and biochemistry of this enzyme are poorly understood, particularly its catalytic mechanism, membrane localization, and structure-function relationships. SOIs from <i>Rhodococcus opacus</i> and <i>Zavarzinia compransoris</i> were produced as SUMO/sfGFP/mCherry fusion proteins. We successfully achieved the overproduction and performed site-directed mutagenesis to understand the catalytic mechanism, performed whole-cell assays, used fluorescent microscopy to assess the membrane localization, and constructed terminal truncations to assess structure-function relationships. The site-directed mutagenesis revealed histidine-57 as the axial ligand for heme. The fluorescence microscopy of sfGFP-fusion showed that SOI is a membrane-bound protein with both termini localized in the cytosol. The difference in activity of differently tagged SOI and truncation of the terminal extension showed that the termini might facilitate proper substrate channelling.</p>","PeriodicalId":18670,"journal":{"name":"Microbiology spectrum","volume":" ","pages":"e0152625"},"PeriodicalIF":3.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145040675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improved time-to-detection with the new formulation of BD BACTEC Plus Aerobic/F Culture Vials: a real-world evidence study.","authors":"Kayla Van Benten, Mondraya Howard, Valentin Parvu, Chris Massey, Stephanie Frey","doi":"10.1128/spectrum.01969-25","DOIUrl":"https://doi.org/10.1128/spectrum.01969-25","url":null,"abstract":"<p><p>BD BACTEC Plus Aerobic/F Culture Vials were modified to reduce time-to-detection (TTD) of bacteria and yeast in blood specimens. Analytical testing involved seeded blood specimens in either predicate plus (N = 500) and modified plus (N = 500) media. Clinical testing used positive aerobic vial results from BD EpiCenter System Software for two periods: predicate plus (N = 1,075) and modified plus medium (N = 873). TTD was measured from the start of vial incubation to microorganism growth detection on BD BACTEC FX. Wilcoxon rank-sum and Chi-square (χ²) tests were used to compare TTD and 48-hour positivity. Modified plus reduced TTD by 2.6 hours (<i>P</i> < 0.001) in analytical testing and 2.9 hours (<i>P</i> < 0.05) in clinical testing. Significant TTD reductions were observed for <i>E. coli</i>, <i>E. faecalis</i>, <i>S. epidermidis</i>, and <i>P. mirabilis</i>. The incidence of late positives (detection after 48 hours) decreased from 10.5% to 6.9%. Modified plus media significantly reduces TTD and the number of late positives for a range of microorganisms.</p><p><strong>Importance: </strong>Faster detection of infectious organisms can help improve patient prognosis. Recently, the formulation of aerobic culture vial media was modified for blood culture on the BD BACTEC instrument. The work presented here provides compelling evidence that the new aerobic media formulation improves time-to-detection for bloodstream infections. This has the potential to impact the healthcare treatment of millions of patients each year without requiring changes in clinical workflow. Faster time to detection can lead to faster organism identification and antimicrobial susceptibility testing (when appropriate). This report provides a comprehensive comparison of the novel media formulation with the predicate formulation for detecting multiple organism genera in both analytical and prospective clinical studies.</p>","PeriodicalId":18670,"journal":{"name":"Microbiology spectrum","volume":" ","pages":"e0196925"},"PeriodicalIF":3.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145040633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of the spoilage microbial communities in plant-based meat alternatives during refrigerated storage.","authors":"Mehmet Dogan, David A Mann, Xiangyu Deng","doi":"10.1128/spectrum.01650-25","DOIUrl":"https://doi.org/10.1128/spectrum.01650-25","url":null,"abstract":"<p><p>Plant-based meat alternatives (PBMAs), primarily derived from pea or soy proteins, are gaining popularity and market share, yet their spoilage ecology remains understudied. To address this knowledge gap, we profiled the bacterial and fungal communities of 12 refrigerated PBMAs commonly sold in the United States (six pea-based meats [PBMs] and six soy-based meats [SBMs], each in ground and burger forms) during refrigerated shelf display and extended storage. Microbial loads rose rapidly and heterogeneously across products after in-store thawing and past sell-by dates, underscoring the need to handle PBMAs like any other highly perishable food, both in stores and at home. Soy and pea-based matrices exhibited distinct patterns of spoilage microbiota assemblage and succession, suggesting that the protein source shapes spoilage trajectories.IMPORTANCEOur findings highlight that spoilage of plant-based meat alternatives (PBMAs) is shaped by the protein source, with soy- and pea-based products exhibiting distinct microbial trajectories and acidity profiles driven by both ingredient composition and spoilage microbiota. Identification of these ingredient-associated spoilage patterns lays the foundation for tailored and precision spoilage management for PBMAs.</p>","PeriodicalId":18670,"journal":{"name":"Microbiology spectrum","volume":" ","pages":"e0165025"},"PeriodicalIF":3.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145040661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular epidemiology and pretreatment drug resistance of HIV-1 among newly diagnosed individuals in Nanning City, Guangxi, China.","authors":"Ting Huang, Jinfeng He, Qiuqian Su, Liangjia Wei, Jiao Qin, Xinju Huang, Chunxing Tao, Fei Zhang, Li Ye, Ping Cen, Hao Liang, Bingyu Liang","doi":"10.1128/spectrum.03149-24","DOIUrl":"https://doi.org/10.1128/spectrum.03149-24","url":null,"abstract":"<p><p>Emerging pretreatment drug resistance (PDR) significantly reduces the effectiveness of HIV antiretroviral therapy (ART). This study assessed the prevalence, associated factors, and transmission networks of PDR among newly diagnosed, ART-naïve individuals in Guangxi, China, from 2019 to 2022. A cross-sectional study was conducted between 2019 and 2022 in Nanning, Guangxi, involving 1,260 newly diagnosed, ART-naïve individuals with HIV. PDR levels and mutations were identified using the Stanford HIV Drug Resistance Database. Multivariable logistic regression models were employed to identify factors associated with PDR and to cluster the molecular network. A total of 1,048 eligible pol sequences were analyzed. The overall prevalence of PDR was 8.4%, with non-nucleoside reverse transcriptase inhibitors (NNRTIs) being the most commonly affected drug class. The most prevalent NNRTI-associated mutation was E138A (2.4%). High-level resistance was primarily observed to efavirenz and nevirapine. The CRF08_BC subtype exhibited significant clustering of PDR-related sequences. Those individuals diagnosed in 2022 were more likely to have PDR. Transmission networks clustering was significantly associated with CRF01_AE and CRF08_BC subtypes, older age, and heterosexual transmission. This study identified a moderate prevalence of PDR among newly diagnosed HIV patients in Guangxi, primarily driven by NNRTI-associated resistance mutations. The pronounced clustering of PDR in the CRF08_BC subtype highlights the need for subtype-specific surveillance and intervention strategies. To improve treatment outcomes and constrain the spread of resistance, targeted educational programs on ART adherence and drug resistance awareness should be prioritized, especially among older adults and individuals infected through heterosexual contacts, alongside enhanced molecular monitoring.</p><p><strong>Importance: </strong>This study highlights the growing challenge of pretreatment drug resistance (PDR) among newly diagnosed individuals with HIV in Nanning City. As antiretroviral therapy (ART) coverage expands, the persistence and transmission of drug-resistant strains pose a significant barrier to long-term treatment success. By documenting trends in PDR and identifying associated factors within a large representative sample, this study offers timely and actionable insights for clinicians and public health policymakers. The identification of key resistance mutations and clustering patterns, particularly in the CRF08_BC subtype, provides a critical foundation for tailored intervention strategies. Overall, these findings address a significant regional data gap and contribute to the optimization of HIV treatment and prevention efforts in China.</p>","PeriodicalId":18670,"journal":{"name":"Microbiology spectrum","volume":" ","pages":"e0314924"},"PeriodicalIF":3.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145040068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assembly of the <i>Mycobacterium tuberculosis</i> type VII ESX-1 secretion system in <i>Mycobacterium smegmatis</i> identifies a new transcriptional activator of <i>esx-1</i> genes and a novel TB vaccine.","authors":"Slim Zriba, Ze Long Lim, Marlene Snider, Nirajan Niroula, Marie Hardouin, Jeffrey M Chen","doi":"10.1128/spectrum.01131-25","DOIUrl":"https://doi.org/10.1128/spectrum.01131-25","url":null,"abstract":"<p><p><i>Mycobacterium tuberculosis</i> (<i>M. tb</i>) uses its type VII secretion system (T7SS) ESX-1 to export immunogenic, virulence-mediating protein effectors. In this study, the fast-growing, non-pathogenic model mycobacteria <i>Mycobacterium smegmatis</i> mc²-155 was engineered to express the <i>M. tb</i> T7SS ESX-1 system. We found that <i>M. smegmatis</i> transformed with <i>M. tb esx-1</i> locus genes only, as well as <i>M. smegmatis</i> transformed with <i>M. tb esx-1</i> and <i>espACD</i> operon genes (designated MSX-1), produces and secretes the <i>M. tb</i> ESX-1 protein effectors EsxA, EsxB, and EspB. However, the abundance of these proteins was higher inside the cell and culture filtrate of the MSX-1 strain. Although ESX-1 is critical for <i>M. tb</i> pathogenesis, expression of <i>M. tb</i> ESX-1 did not make the recombinant <i>M. smegmatis</i> strains virulent in macrophages. Serendipitously, transformation of <i>M. smegmatis</i> with a modified <i>esx-1</i> locus in this study revealed <i>rv3860</i>, a gene of previously unknown function, to be required for the transcription of <i>pe35</i>, <i>ppe68</i>, <i>esxB,</i> and <i>esxA</i> genes. Finally, mice vaccinated with MSX-1 were found to be as protected as mice vaccinated with <i>Mycobacterium bovis</i> BCG against <i>M. tb</i> infection, without becoming sensitized to tuberculin. These results show that a functional <i>M. tb</i> ESX-1 system can be assembled in <i>M. smegmatis</i> to uncover novel facets of the secretion machinery and that the modified <i>M. smegmatis</i> strain can function as a tuberculosis (TB) vaccine. Unlike BCG, however, its deployment may be compatible with tests currently used to diagnose TB.IMPORTANCEIn this study, we modified <i>Mycobacterium smegmatis</i>, which is often used as a surrogate model organism in mycobacterial research, to produce and assemble a functional <i>Mycobacterium tuberculosis</i> (<i>M. tb</i>) ESX-1 protein secretion system. One such <i>M. smegmatis</i> strain named MSX-1 was found to make a functional <i>M. tb</i> ESX-1 system without becoming virulent. And in using <i>M. smegmatis</i> as a chassis to study the ESX-1 system, we found that <i>rv3860</i>, an <i>M. tb</i> gene of previously unknown function, is needed for the production of key ESX-1 proteins. Finally, mice vaccinated with MSX-1 were as protected from tuberculosis (TB) as mice given BCG, the only approved TB vaccine. Notably, we found that unlike BCG, MSX-1 does not sensitize mice to the antigens used in existing TB diagnostic tests. These observations, taken together, highlight the utility of <i>M. smegmatis</i> as a chassis to study the <i>M. tb</i> ESX-1 secretion machinery.</p>","PeriodicalId":18670,"journal":{"name":"Microbiology spectrum","volume":" ","pages":"e0113125"},"PeriodicalIF":3.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145040690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Teropavimab and zinlirvimab sensitivity in people living with multidrug-resistant HIV-1: data from the PRESTIGIO Registry.","authors":"Vincenzo Spagnuolo, Laura Galli, Jiani Li, Keith Dunn, Filippo Lagi, Roberta Gagliardini, Loredana Sarmati, Anna Maria Cattelan, Andrea Giacomelli, Maria Mercedes Santoro, Maurizio Zazzi, Christian Callebaut, Antonella Castagna, Laurie A VanderVeen","doi":"10.1128/spectrum.02777-24","DOIUrl":"https://doi.org/10.1128/spectrum.02777-24","url":null,"abstract":"<p><p>We characterized sensitivity to teropavimab (TAB) and zinlirvimab (ZAB) in people living with four-class drug-resistant HIV (4DR-PWH). This was a multicenter, observational study using plasma or peripheral blood mononuclear cells collected from 50 4DR-PWH (25 with HIV-1 RNA > 1,000 copies/mL matched by age, sex, nadir CD4+, and years on ART to 25 virologically suppressed [HIV-1 RNA < 50 copies/mL]) enrolled in the PRESTIGIO Registry (NCT04098315) with a documented 4DR (NRTIs, NNRTIs, PIs, and INSTIs). Phenotypic sensitivity to bNAbs was determined using the PhenoSense monoclonal antibody assay (Monogram), with susceptibility defined as IC₉₀ ≤ 2 µg/mL. The HIV-1 envelope was genotyped by next-generation sequencing, and sequences were analyzed for the presence of multi-position HIV-1 envelope amino acid signatures associated with <i>in vitro</i> phenotypic susceptibility to TAB and ZAB. Of 46/50 (92%) participants with PhenoSense mAb assay results, 35 (76%) were phenotypically sensitive to TAB, 23 (50%) to ZAB, and 19 (41%) to both bNAbs; seven (15%) were phenotypically resistant to both bNAbs. The proportion of individuals with sensitivity to both bNAbs was similar in participants with viremia (41%) and those with virologic suppression (42%; <i>P</i> = 0.99). We observed marginal correlations between TAB 90% inhibitory concentration (IC₉₀) values and years since HIV diagnosis at the time of sample collection (<i>Spearman</i> r = 0.29, <i>P</i> = 0.05) as well as between ZAB IC₉₀ values and CD8+ cell count (<i>Spearman</i> r = -0.32, <i>P</i> = 0.05). A significant number of the 4DR-PWH analyzed were found to have virus susceptible to TAB and ZAB. These data provide proof-of-concept that selected multidrug-resistant PWH may be candidates for future trials investigating bNAbs-containing regimens to achieve or maintain virologic suppression.IMPORTANCEMultidrug-resistant HIV presents significant challenges for treatment, often leaving individuals with a limited range of therapeutic alternatives. This study provides crucial insights into the efficacy of two promising broadly neutralizing antibodies, teropavimab (TAB) and zinlirvimab (ZAB), in individuals living with HIV who have developed resistance to multiple drug classes. The findings indicate that a significant proportion of the population remains susceptible to these novel treatments, irrespective of their viral suppression status. These results offer a promising basis for developing new therapeutic strategies to improve outcomes for individuals with multidrug-resistant HIV who have a history of extensive treatment, paving the way for future clinical trials aimed at achieving long-term viral suppression with novel drug regimens.</p>","PeriodicalId":18670,"journal":{"name":"Microbiology spectrum","volume":" ","pages":"e0277724"},"PeriodicalIF":3.8,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145033776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}